Scientists Substitute Oncogene with Protein to Transform Adult Cells into Embryonic-Like State in Mice

Researchers from Whitehead Institute for Biomedical Research have found a replacement to the oncogene needed to reprogram adult cells to an embryonic stem cell like state. They report that using mice, they were able to successfully replace cancer promoter c-Myc, which is one of four genes required for this process, with a protein called Wnt.

These embryonic stem cell like cells are also known as induced pluripotent (IPS) cells. Currently, retroviruses are used to transfer the four genes—Oct4, Sox2, c-Myc, and Klf4—into the cells' DNA for reprogramming.

This method, however, poses significant risks for potential use in humans, according to the researchers. Retroviruses are associated with cancer because they insert DNA anywhere in a cell's genome, thereby potentially triggering the expression of cancer-causing genes. Additionally, c-Myc is a known oncogene whose overexpression can also cause cancer.

Earlier research has shown that c-Myc is not strictly required for the generation of IPS cells. Its absence, however, makes the reprogramming process time consuming and highly inefficient, the investigators point out.

To bypass these obstacles, the Whitehead researchers replaced c-Myc and its retrovirus with Wnt3a. When added to the fluid surrounding the cells being reprogrammed, they found that Wnt3a promotes the conversion of adult cells into IPS cells.

These findings are published in the August 7 online issue of Cell Stem Cell.

“We're not sure if the Wnt molecule is doing the same thing as c-Myc or complementing c-Myc's activity,” says Brett Chevalier, a research scientist involved in this study. “But it does increase stem cell growth similar to c-Myc.”

Although the technique is promising in mouse cells, its potential applications in humans have not been studied, emphasizes Rudolf Jaenisch, a lead coauthor on the paper and professor of biology at MIT. He says that work needs to be done to figure out whether the same pathway acts in the human system and if Wnt molecules can be used to reprogram human cells.